Water-and organic-soluble cucurbituril derivatives, their preparation methods, their separation methods and uses

ABSTRACT

Provided are cucurbituril derivatives having the formula (1), their preparation methods and uses: 
                         
where X is O, S or NH; R 1  and R 2  are each independently selected from the group consisting of hydrogen, alkyl groups of 1 to 30 carbon atoms, alkenyl groups of 1 to 30 carbon atoms, alkynyl groups of 1 to 30 carbon atoms, alkylthio groups of 1 to 30 carbon atoms, alkylcarboxyl groups of 1 to 30 carbon atoms, hydroxyalkyl groups of 1 to 30 carbon atoms, alkylsilyl groups of 1 to 30 carbon atoms, alkoxy groups of 1 to 30 carbon atoms, haloalkyl groups of 1 to 30 carbon atoms, nitro group, alkylamine groups of 1 to 30 carbon atoms, amine group, aminoalkyl groups of 1 to 30 carbon atoms, unsubstituted cycloalkyl groups of 5 to 30 carbon atoms, cycloalkyl groups of 4 to 30 carbon atoms with hetero atoms, unsubstituted aryl groups of 6 to 30 carbon atoms, and aryl groups of 6 to 30 carbon atoms with hetero atoms; and n and m are independently integers from 4 to 20 and from 1 to 7, respectively. The cucurbituril derivative has enhanced solubility in common solvents, thereby providing wider applications.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to water- and organic-soluble cucurbiturilderivatives, their preparation methods, their separation methods anduses, and more particularly, to novel cucurbituril derivatives havingvarious repeating units and internal cavities of various sizes and beingsoluble in pure water at a neutral pH or in common organic solvents,their preparation methods, methods of separating pure cucurbiturilderivatives, and their uses.

2. Description of the Related Art

Cucurbituril is a compound whose preparation was first reported byBehrend et al. in 1905 (Liebigs Ann. Chem. 1905, 339, 1). According totheir report, the condensation of glycoluril and excess formaldehyde inthe presence of hydrochloric acid (HCl) produces an amorphous solid.Dissolution of the solid in hot concentrated sulfuric acid, dilution ofthe solution with water followed by slow cooling of the solution to roomtemperature produces a crystalline material. They wrongly characterizedthis substance as C₁₀H₁₁N₇O₄·2H₂O, whose structure was, however, not yetidentified.

In 1981, this substance was rediscovered by Mock and coworkers. Theycorrectly characterized it as a hexameric macrocyclic compound withcomposition of C₃₆H₃₆N₂₄O₁₂, which was also confirmed by X-ray crystalstructure determination (J. Am. Chem. Soc., 1981, 103, 7367). They namedit cucurbituril which we from now on refer to as cucurbit[6]uril. Sincethen an improved preparation procedure for cucurbit[6]uril has beendisclosed (DE 196 03 377 A1).

In 2000, the conventional preparation method of cucurbit[6]uril wasimproved by Kimoon Kim and coworkers to synthesize and separatecucurbit[6]uril and its homologue cucurbitu[n]uril (n=5, 7 and 8), whichwas confirmed by X-ray crystal structure determination (J. Am. Chem.Soc., 2000, 122, 540).

The above-described cucurbituril derivatives are compounds ofunsubstituted glycoluril monomers and are disadvantageously soluble onlyin an aqueous acidic solution.

As a cucurbituril derivative with a substitutent other than hydrogen,decamethylcucurbit[5]uril, in which five dimethanodimethylglycolurilunits form a cyclic structure by the condensation of dimethylglycoluriland formaldehyde, has only been reported (Angew. Chem. Int. Ed. Engl.1992, 31, 1475). However, this compound is also soluble only in anaqueous acidic solution.

As described above, the cucurbituril derivatives that have been preparedand known up to now are very limited in terms of their applicationsbecause they are insoluble in pure water at a neutral pH or commonorganic solvents such as methanol.

International Patent Publication WO 00/68232 discloses cucurbit[n]urilhaving the following formula:

where n is a value of 4 to 12.

In addition, WO 00/68232 discloses substituted glycoluril derivativeshaving the following formulas:

However, cucurbituril derivatives prepared from the above-describedglycoluril derivatives are not disclosed in the cited reference. Also,since the glycoluril derivatives have considerably large substituents,it is quite difficult to synthesize cucurbituril derivativescorresponding thereto due to steric hindrance.

SUMMARY OF THE INVENTION

To solve the above-described problems, the first objective of thepresent invention is to provide novel cucurbituril derivatives havingvarious sized cavities and/or having enhanced solubilities in commonsolvents, and novel glycoluril derivatives used in preparing thecucurbituril derivatives.

The second objective of the present invention is to provide methods ofpreparing the cucurbituril derivatives and the glycoluril derivatives.

The third objective of the present invention is to provide methods ofseparating pure cucurbituril derivatives from a mixture of thecucurbituril derivatives.

The fourth objective of the present invention is to provide the uses ofthe cucurbituril derivatives.

The first objective of the present invention is achieved by cucurbiturilderivatives having the formula (1):

where X is O, S or NH; R₁, and R₂ are each independently selected fromthe group consisting of hydrogen, alkyl groups of 1 to 30 carbon atoms,alkenyl groups of 1 to 30 carbon atoms, alkynyl groups of 1 to 30 carbonatoms, alkylthio groups of 1 to 30 carbon atoms, alkylcarboxyl groups of1 to 30 carbon atoms, hydroxyalkyl groups of 1 to 30 carbon atoms,alkylsilyl groups of 1 to 30 carbon atoms, alkoxy groups of 1 to 30carbon atoms, haloalkyl groups of 1 to 30 carbon atoms, nitro group,alkylamine groups of 1 to 30 carbon atoms, amine group, aminoalkylgroups of 1 to 30 carbon atoms, unsubstituted cycloalkyl groups of 5 to30 carbon atoms, cycloalkyl groups of 4 to 30 carbon atoms with heteroatoms, unsubstituted aryl groups of 6 to 30 carbon atoms, and arylgroups of 6 to 30 carbon atoms with hetero atoms; and n and m areindependently integers from 4 to 20 and from 1 to 7, respectively.

According to another aspect of the present invention, there is provideda glycoluril derivative having the formula (2):

where X is O, S or NH; R₁is independently selected from the groupconsisting of hydrogen, alkyl groups of 1 to 30 carbon atoms, alkenylgroups of 1 to 30 carbon atoms, alkynyl groups of 1 to 30 carbon atoms,alkylthio groups of 1 to 30 carbon atoms, alkylcarboxyl groups of 1 to30 carbon atoms, hydroxyalkyl groups of 1 to 30 carbon atoms, alkylsilylgroups of 1 to 30 carbon atoms, alkoxy groups of 1 to 30 carbon atoms,haloalkyl groups of 1 to 30 carbon atoms, nitro group, alkylamine groupsof 1 to 30 carbon atoms, amine group, aminoalkyl groups of 1 to 30carbon atoms, unsubstituted cycloalkyl groups of 5 to 30 carbon atoms,cycloalkyl groups of 4 to 30 carbon atoms with hetero atoms,unsubstituted aryl groups of 6 to 30 carbon atoms, and aryl groups of 6to 30 carbon atoms with hetero atoms; and m is an integer from 1 to 7,exclusive of 4.

The second objective of the present invention is achieved by a methodfor preparing a cucurbituril derivative having the formula (1),including (a-2) mixing and stirring a compound having the formula (2)and an aldehyde compound having the formula (A), and (b-2) adding acidto the reaction mixture and stirring to complete the reaction,

where X is O, S or NH; R₁ and R₂ are each independently selected fromthe group consisting of hydrogen, alkyl groups of 1 to 30 carbon atoms,alkenyl groups of 1 to 30 carbon atoms, alkynyl groups of 1 to 30 carbonatoms, alkylthio groups of 1 to 30 carbon atoms, alkylcarboxyl groups of1 to 30 carbon atoms, hydroxyalkyl groups of 1 to 30 carbon atoms,alkylsilyl groups of 1 to 30 carbon atoms, alkoxy groups of 1 to 30carbon atoms, haloalkyl groups of 1 to 30 carbon atoms, nitro group,alkylamine groups of 1 to 30 carbon atoms, amine group, aminoalkylgroups of 1 to 30 carbon atoms, unsubstituted cycloalkyl groups of 5 to30 carbon atoms, cycloalkyl groups of 4 to 30 carbon atoms with heteroatoms, unsubstituted aryl groups of 6 to 30 carbon atoms, and arylgroups of 6 to 30 carbon atoms with hetero atoms; and n and m areindependently integers from 4 to 20 and from 1 to 7, respectively.

In step (a-2), the acid is preferably added in an amount of 3 to 7 molesand the aldehyde compound having the formula (A) is preferably added inan amount of 2 to 20 moles with respect to 1 mole of the compound havingthe formula (2), and the reaction temperature is preferably in the rangeof 50 to 150° C. Also, in step (b-2), the reaction temperature ispreferably in the range of 50 to 150° C.

Among reaction products of step (b-2), the cucurbituril derivative withn=5 is preferably produced in a yield of 15 to 50%, the cucurbiturilderivative with n=6 is preferably produced in a yield of 2 to 10%, andthe cucurbituril derivatives with n=4 and 7 to 20 are preferablyproduced in a yield of 1 to 5%, respectively.

According to another aspect of the present invention, there is provideda method for preparing a glycoluril derivative having the formula (2):

where X is O, S or NH; R₁ and R₂ are each independently selected fromthe group consisting of hydrogen, alkyl groups of 1 to 30 carbon atoms,alkenyl groups of 1 to 30 carbon atoms, alkynyl groups of 1 to 30 carbonatoms, alkylthio groups of 1 to 30 carbon atoms, alkylcarboxyl groups of1 to 30 carbon atoms, hydroxyalkyl groups of 1 to 30 carbon atoms,alkylsilyl groups of 1 to 30 carbon atoms, alkoxy groups of 1 to 30carbon atoms, haloalkyl groups of 1 to 30 carbon atoms, nitro group,alkylamine groups of 1 to 30 carbon atoms, amine group, aminoalkylgroups of 1 to 30 carbon atoms, unsubstituted cycloalkyl groups of 5 to30 carbon atoms, cycloalkyl groups of 4 to 30 carbon atoms with heteroatoms, unsubstituted aryl groups of 6 to 30 carbon atoms, and arylgroups of 6 to 30 carbon atoms with hetero atoms; and m is an integerfrom 1 to 7, exclusive of 4, the method including (a-1) adding anaqueous acidic solution or an acid-containing organic solvent to amixture of a urea derivative (B) and a cyclodione compound (C) forreaction, and (b-1) removing water or the organic solvent from thereaction mixture.

In step (a-1), the reaction temperature is preferably in the range of 70to 120° C. Preferably, the amount of the cyclodione compound (C) used inthe reaction is 0.1 to 0.5 moles for each mole of the urea derivative(B). Also, the aqueous acidic solution is preferably selected from thegroup consisting of trifluoroacetic acid, methane sulfonic acid, aceticacid, hydrochloric acid, nitric acid and sulfuric acid, and theacid-containing organic solvent is selected from the group consisting ofbenzene and toluene.

To accomplish the third objective, the present invention provides amethod of separating the cucurbituril derivative having the formula (1)from the cucurbituril derivative mixture by a fractionalcrystallization. The fractional crystallization procedure is based ondifferent solubilities in at least one solvent selected from the groupconsisting of water, acetone and acetonitrile.

The fourth objective of the present invention is achieved by a methodfor using the cucurbituril derivative to remove organic dyes from wastewater, heavy metal from water, and radioactive isotopes from radioactivewastes, to capture and remove unpleasant odor, and air pollutants, andto deodorize and decolorize livestock waste water and ironwork wastewater. Alternatively, the present invention can be used for sensors forsensing ammonium ions, organic amines, amino acid derivatives, nucleicacid bases, alkali metal or alkaline earth metal ions, additives topolymers, cosmetics, artificially scented papers or textiles, pesticidesand herbicides, drugs, and drug carriers. Further, the present inventioncan be used for extraction and purification of fullerene or caboranecompounds, and used as packing materials of chromatographic columns, asadditives to gas separation membranes, as catalysts for various chemicalreactions. In particular, in a preferred embodiment of the presentinvention, there is provided an ion sensor employing the cucurbiturilderivative as an ion selective material.

The cucurbituril derivatives according to the present invention arerepresented by the formula (1):

where X is O, S or NH; R₁ and R₂ are independently selected from thegroup consisting of hydrogen, alkyl groups of 1 to 30 carbon atoms,alkenyl groups of 1 to 30 carbon atoms, alkynyl groups of 1 to 30 carbonatoms, alkylthio groups of 1 to 30 carbon atoms, alkylcarboxyl groups of1 to 30 carbon atoms, hydroxyalkyl groups of 1 to 30 carbon atoms,alkylsilyl groups of 1 to 30 carbon atoms, alkoxy groups of 1 to 30carbon atoms, haloalkyl groups of 1 to 30 carbon atoms, nitro group,alkylamine groups of 1 to 30 carbon atoms, amine group, aminoalkylgroups of 1 to 30 carbon atoms, unsubstituted cycloalkyl groups of 5 to30 carbon atoms, cycloalkyl groups of 4 to 30 carbon atoms with heteroatoms, unsubstituted aryl groups of 6 to 30 carbon atoms, and arylgroups of 6 to 30 carbon atoms with hetero atoms; and n and m areindependently integers from 4 to 20 and from 1 to 7, respectively.

The alkyl groups of 1 to 30 carbon atoms for R₁ and R₂ may includemethyl, ethyl, propyl, isopropyl and t-butyl groups. The alkenyl groupsof 1 to 30 carbon atoms for R₁ and R₂ may include propylene and butenegroups, and the alkynyl groups of 1 to 30 carbon atoms therefore mayinclude a hexynyl group. The alkylthio groups of 1 to 30 carbon atomsmay include butylmethylsulfide and octanethiol groups. The alkylcarboxylgroups of 1 to 30 carbon atoms may include carboxypropyl andcarboxylbutyl groups. The hydroxylalkyl groups of 1 to 30 carbon atomsmay include hydroxybutyl and hydroxyethyl groups. The alkylsilyl groupsof 1 to 30 carbon atoms may include aryltriethylsilyl andvinyltriethylsilyl groups, and the alkoxy groups of 1 to 30 carbon atomsmay include methoxy and ethoxy groups. The haloalkyl groups of 1 to 30carbon atoms may include CF₃ and CH₂Cl, the alkylamine groups of 1 to 30carbon atoms may include methylamine and ethylamine groups, and theaminoalkyl groups of 1 to 30 carbon atoms may include 2-aminobutyl and1-aminobutyl groups. The unsubstituted cycloalkyl groups of 5 to 30carbon atoms may include cyclohexyl and cyclopentyl groups, and thecycloalkyl groups of 4 to 30 carbon atoms with hetero atoms may includepiperidyl and tetrahydrofuranyl groups. The unsubstituted aryl groups of6 to 30 carbon atoms may include phenyl, benzyl and naphthyl groups, andthe aryl groups of 6 to 30 carbon atoms with hetero atoms may includepentafluorophenyl and pyridyl groups.

In consideration of the above examples of R₁ and R₂ in the formula (1)hereinabove, the following compounds may be examples of the cucurbiturilderivatives having the formula (1).

In other words, in the formula (1) hereinabove, R₁ may be hydrogen,methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, phenyl orpyridyl group, and R₂ may be hydrogen, methyl, propyl, phenyl,trichloromethyl, trifluoromethyl, parafluorophenyl or α, α,α-trifluorotolyl group. Alternatively, R₁ may be hydrogen, and R₂ may behydrogen, methyl, ethyl, propyl, phenyl, trichloromethyl,trifluoromethyl, parafluorophenyl or α, α, α-trifluorotolyl group. Inanother embodiment, R₁ may be methyl group, and R₂ may be hydrogen,methyl, ethyl, propyl, phenyl, trichloromethyl, trifluoromethyl,parafluorophenyl or α, α, α-trifluorotolyl group. More preferablecucurbituril derivatives have the formula (1) hereinabove, wherein X=O,R₁ and R₂ are both hydrogens, n is a value of 4 to 20 and m is a valueof 1 to 7, and wherein X=NH or S, R₁ and R₂ are both hydrogens, n is avalue of 4 to 20 and m is a value of 1 to 7.

In particular, the cucurbituril derivatives according to the presentinvention wherein n=5, m=4, X=O and R₁ and R₂ are both hydrogens, havehigh solubilities, that is, 1×10⁻¹ to 3×10⁻¹ M in water, and 1×10⁻⁴ to1×10⁻²M in an organic solve selected from the group consisting ofmethanol, ethanol, dimethylsulfoxide, dimethylformamide andacetonitrile. As described above, the cucurbituril derivatives accordingto the present invention are soluble in common solvents, therebyproviding wider applications.

Alternatively, the present invention provides glycoluril derivativeshaving the formula (2), and is used for preparing a cucurbiturilderivative having the formula (1):

where X is O, S or NH; R₁ is independently selected from the groupconsisting of hydrogen, alkyl groups of 1 to 30 carbon atoms, alkenylgroups of 1 to 30 carbon atoms, alkynyl groups of 1 to 30 carbon atoms,alkylthio groups of 1 to 30 carbon atoms, alkylcarboxyl groups of 1 to30 carbon atoms, hydroxyalkyl groups of 1 to 30 carbon atoms, alkylsilylgroups of 1 to 30 carbon atoms, alkoxy groups of 1 to 30 carbon atoms,haloalkyl groups of 1 to 30 carbon atoms, nitro group, alkylamine groupsof 1 to 30 carbon atoms, amine group, aminoalkyl groups of 1 to 30carbon atoms, unsubstituted cycloalkyl groups of 5 to 30 carbon atoms,cycloalkyl groups of 4 to 30 carbon atoms with hetero atoms,unsubstituted aryl groups of 6 to 30 carbon atoms, and aryl groups of 6to 30 carbon atoms with hetero atoms; and m is an integer from 1 to 7,exclusive of 4.

In R₁ of the formula 2, the alkyl groups of 1 to 30 carbon atoms,alkenyl groups of 1 to 30 carbon atoms, alkynyl groups of 1 to 30 carbonatoms, alkylthio groups of 1 to 30 carbon atoms, alkylcarboxyl groups of1 to 30 carbon atoms, hydroxyalkyl groups of 1 to 30 carbon atoms,alkylsilyl groups of 1 to 30 carbon atoms, alkoxy groups of 1 to 30carbon atoms, haloalkyl groups of 1 to 30 carbon atoms, alkylaminegroups of 1 to 30 carbon atoms, aminoalkyl groups of 1 to 30 carbonatoms, unsubstituted cycloalkyl groups of 5 to 30 carbon atoms,cycloalkyl groups of 4 to 30 carbon atoms with hetero atoms,unsubstituted aryl groups of 6 to 30 carbon atoms, and aryl groups of 6to 30 carbon atoms with hetero atoms, are exemplified as defined above.More preferably, the cucurbituril derivatives have the formula (2)hereinabove, wherein m=3 or 4, R₁ and R₂ are both hydrogens.

Hereinafter, the methods for synthesizing the cucurbituril derivativeshaving the formula (1) according to the present invention will bedescribed, as represented by the reaction schemes (1) and (2).

An acid is added to the glycoluril derivative having the formula (2) inan amount of 3 to 7 moles with respect to 1 mole thereof, and mixed.Preferably, the acid is diluted with water or an organic solvent to be 1to 12M, more preferably to be 6 to 12M. Any acid capable of dissolvingthe glycoluril derivative having the formula (2), for example, can beused, and usable acids include hydrochloric acid, sulfuric acid,phosphoric acid, acetic acid, nitric acid and an mixtures of theseacids. The organic solvent as an acid diluent may be dimethylsulfoxide,N,N-dimethylformamide, methanol, ethanol, chloroform or an mixture ofthese solvents.

The compound having the formula (2) (X=O) can be synthesized by thefollowing method.

A urea derivative (B) (Y=O), that is, urea, and a cyclodione compound(C) (m=1–7) are dissolved in an aqueous acidic solution or anacid-containing organic solvent, and stirred for a certain period oftime. In this step, the reaction temperature is preferably in the rangeof 70 to 120° C. Failure to fall within the above range isdisadvantageous from the viewpoint of reactivity. The content of thecyclodione compound (C) is preferably in the range of 0.1 to 0.5 molewith respect to 1 mole of the urea derivative (B).

The aqueous acidic solution is obtained from acid selected from thegroup consisting of trifluoroacetic acid, methane sulfonic acid, aceticacid, hydrochloric acid, nitric acid and sulfuric acid. Theacid-containing organic solvent is selected from the group consisting ofbenzene and toluene.

Removal of water or the organic solvent from the reaction mixtureproduces the compound having the formula (2) (X=O). The compound havingthe formula (2) with X=S or NH can be obtained by a similar procedure.

where m and R₁ are as defined above.

Next, as shown in the reaction scheme 2, an aldehyde compound A is addedto the reaction mixture of the compound having the formula (2) (X=O) andan acid and reacted while stirring at 50 to 150° C. for 30 minutes to 1hour. If the reaction temperature is lower than 50° C., little reactionis occurred. If the reaction temperature is beyond 150° C.,decomposition of a viscous intermediate reaction product may undesirablyoccur.

The amount of the aldehyde compound (A) used in the reaction is 2 to 20moles for each mole of the compound having the formula 2, preferably 4moles. Detailed examples of the aldehyde compound (A) includeformaldehyde, acetaldehyde, propionaldehyde, benzaldehyde, and the like.

wherein m, n, R₁ and R₂ are as defined above.

During the reaction, the color of the reaction solution changes intodark red and the viscosity thereof increases, with time.

Excess acid is further added to the reaction mixture, followed byfurther reacting at 50 to 150° C. for 24 hours, completing the reaction.After addition of excess acid, if the reaction temperature is lower than50° C., little reaction is occurred. If the reaction temperature isbeyond 150° C., decomposition of a viscous intermediate reaction productmay undesirably occur.

The final reaction product varies depending on the reaction temperatureand the amount of reactants. The final reaction product is a mixture oftwo or more cucurbituril derivatives described above, where n is a valuefrom 4 to 20, irrespective of m.

Typically, the reaction product is a mixture of the cucurbiturilderivatives where n=4 to, 20 and m=1 to 7. Here, the cucurbiturilderivative with n=5 is produced in a yield of 15 to 50%, thecucurbituril derivative with n=6 is produced in a yield of 2 to 10%, andthe cucurbituril derivatives with n=4 and 7 to 20 are produced in ayield of 1 to 5%.

Then, the resulting cucurbituril derivatives are separated from eachother by a fractional crystallization procedure. The separation stepusing the fractional crystallization procedure is based on differentsolubilities in solvents of water, acetone, acetonitrile and so on.

A method of synthesizing the cucurbituril derivatives having the formula(1) with X=S will now be described. The cucurbituril derivatives havingthe formula (1) with X=S can also be synthesized by the above-describedmethods using the compound having the formula (2) with X=S, instead ofwith X=O. Here, the compound having the formula (2) with X=S can besynthesized in the same way described previously, except that thioureainstead of urea is used. Furthermore, the above-described methods can beapplied in synthesizing the cucurbituril derivatives with X=NH.

As described above, the present invention provides easy preparationmethods for the cucurbituril derivatives having the formula (1), where nranges from 5 to 20, and desired cucurbituril derivatives can beobtained in pure types using different solubilities in a common solvent.Also, according to the present invention, mixtures of two or morecucurbituril derivatives selected from the cucurbituril derivativeshaving the formula (1), where n ranges from 4 to 20, can be easilyobtained.

The cucurbituril derivatives having the formula (1) disclosed by thepresent invention, which can be used as a substitute for cyclodextrin,have cavities having a diameter of 4 to 15 Å, which are able to includeguest molecules, such as cyclic benzene derivatives, naphthalenederivatives, carborane derivatives, fullerene derivatives, ferrocenederivatives and adamantane derivatives in their cavities.

As described above, the cucurbituril derivatives having the formula (1)can encapsulate various compounds with different sizes, and have Lewisbase atoms near the cavities of the molecule, which can interact withcharged metal ions, organometallic ions or organic compounds, and thusthe cucurbituril derivatives can have a wide range of applications. Inparticular, the cucurbituril derivatives having the formula (1)according to the present invention can be used to remove organic dyesfrom waste water, heavy metal from water, and radioactive isotopes fromradioactive wastes, to capture and remove unpleasant odor, and airpollutants such as carbon monoxide, carbon dioxide, NO_(x) and SO_(x),and to deodorize and decolorize livestock waste water and ironwork wastewater. Also, the cucurbituril derivatives having the formula (1) areapplicable in manufacturing sensors for sensing ammonium ions, organicamines, amino acid derivatives, nucleic acid bases, alkali metal oralkaline earth metal ions. The cucurbituril derivatives having theformula (1) can be used as additives to polymers, cosmetics,artificially scented papers or textiles, pesticides and herbicides, anddrugs, and used as drug carriers. The cucurbituril derivatives havingthe formula (1) can be used for extraction and purification of fullereneor caborane compounds, and used as packing materials of chromatographiccolumns, as additives to gas separation membranes, as catalysts forvarious chemical reactions.

In the applications of the cucurbituril derivatives disclosed by thepresent invention, the types of the cucurbituril derivatives are notspecially limited. That is, a certain pure cucurbituril derivative or amixture of cucurbituril derivatives can be used. However, if thedifference in effect is not great among types of the cucurbiturilderivatives used, use of the mixture of cucurbituril derivativesprepared by the reaction schemes 1 and 2 is preferred in terms of cost,because it does not need additional separation process.

An ion sensor employing the cucurbituril derivatives having the formula(1) will now be described.

An ion sensor includes an ion selective membrane. The ion selectivemembrane is formed by dissolving an ion selective material, a polymersupport and a plasticizer in a solvent to prepare a composition forforming an ion selective membrane, and removing the solvent therefrom.An ion selective electrode can be formed using the ion selectivemembrane. Then, an ion sensor can be manufactured using the ionselective electrode by a common method.

In the composition for forming an ion selective membrane, usable ionselective materials include the cucurbituril derivatives having theformula (1). Here, the compound may be used in the form of a mixturewhere n=4 to 20 and m=1 to 7. The polymer support serves to support theion selective membrane and usable examples thereof includepolyvinylchloride, polyurethane and silicon rubber. The amount of thepolymer support used is preferably 1 to 180 parts by weight based on 1part by weight of the ion selective material. Here, if the amount of thepolymer support is out of the above range, the efficiency of the ionsensor is poor.

In the composition for forming an ion selective membrane, theplasticizer serves to improve layer processibility and usable examplesthereof include 2-nitrophenyloctylether, dioctyl adipate and dioctylsebacate. The amount of the plasticizer used is preferably 1 to 140parts by weight based on 1 part by weight of the ion selective material.Here, if the amount of the plasticizer is out of the above range, thelayer processibility may deteriorate.

In some case, an additive for enhancing sensitivity of the ion sensormay be further included in the composition for forming an ion selectivemembrane. Examples of the additive include potassiumtetrakis(4-chlorophenyl)borate, sodiumtetrakis[3,5-bis(1,1,1,3,3,3-hexafluoro-2-methoxy-2-propyl)-phenyl]borateand potassium tetrakis[3,5-bis(trifluoromethyl)-phenyl]borate.

The ion sensor manufactured by the above-described method is used todetect heavy metals such as lead, mercury, alkaline earth metal oralkali metal, or organic matter such as acetylcholine, ammonium ions,organic amines, amino acid, derivatives thereof or nucleic acid bases.

The cucurbituril derivatives used in the ion sensor can be of the typeof a pure compound or a mixture.

BRIEF DESCRIPTION OF THE DRAWINGS

The above and other features and advantages of the present inventionwill become more apparent by describing in detail exemplary embodimentsthereof with reference to the attached drawings in which:

FIG. 1 is a diagram illustrating the X-ray crystal structures ofcucurbituril derivatives prepared in Synthesis Example 1 of the presentinvention;

FIG. 2 is a diagram illustrating the X-ray crystal structures ofcucurbituril derivatives prepared in Synthesis Example 2 of the presentinvention;

FIG. 3 is a graphical representation of lead ions, potassium ions,ammonium ions and sodium ions sensed from an ion selective electrodeprepared using a cucurbituril derivative CB*[5] prepared in SynthesisExample 1 of the present invention; and

FIG. 4 is a graphical representation of lead ions, potassium ions,ammonium ions and sodium ions sensed from an ion selective electrodeprepared using a cucurbituril derivative CB*[6] prepared in SynthesisExample 2 of the present invention.

DETAILED DESCRIPTION OF THE INVENTION SYNTHESIS EXAMPLE 1 Preparation ofthe Cucurbituril Derivative Having the Formula (1) where n=5, m=4, X=O,R₁=R₂=H

1.9 ml of a 30% formaldehyde aqueous solution and 2.0 g of theglycoluril derivative having the formula (2) with m=4, X=O and R₁=H,were mixed and 0.16 ml of 37% aqueous hydrochloric acid solution wasadded thereto. The reaction mixture was stirred at 80° C. for 30minutes. Then, 5 ml of water and. 2.5 ml of sulfuric acid were added andthe reaction mixture was further stirred at 80° C. for 24 hours. Afterthe reaction was completed, the resulting solution) was cooled to roomtemperature and diluted with 10 ml of water. Then, 300 ml of acetone wasadded to the reaction mixture to form a precipitate. The obtainedprecipitate was filtered, washed with acetone and dissolved again in 50ml of water. The resulting solution was neutralized with triethylamineand concentrated under a reduced pressure to afford the solid mixtureswhich consisted of 45% of the cucurbituril derivative with. n=5, 15% ofthe cucurbituril derivative with n=6, 5% of the cucurbituril derivativeswith n=4 and 7 to 20, and so on). The solid mixtures was washed with 20ml of acetonitrile and recrystallized with water or a mixture of waterand acetone to give a colorless crystalline cucurtbituril derivativehaving the formula (1) where n=5, m=4, X=O and R₁=R₂=H (to be termed“CB*[5]” hereinbelow) in 40% yield.

The crystal structure of the obtained cucurbituril derivative wasdetermined by X-ray crystallography. The result is shown in FIG. 1. Asshown in FIG. 1, it was confirmed that the cucurbituril derivativeobtained in Synthesis Example 1 had internal cavities.

¹ H NMR (300 MHz, D₂O): δ=5.64 (d, J=15.6 Hz, 10H), 4.33 (d, J=15.8 Hz,10H), 2.20 (s, 20H), 1.46 (s, 20H); ¹³C NMR (75 MHz, D₂O): δ=156.33,76.45, 43.51, 23.56, 14.0.

SYNTHESIS EXAMPLE 2 Preparation of the Cucurbituril Derivative Havingthe Formula (1) where n=6, m=4, X=O, R₁=R₂=H

The solid mixtures obtained from a solution filtered with 20 ml ofacetonitrile in Synthesis Example 1 was recrystallized with water or amixture of water and acetone to give a colorless crystallinecucurtbituril derivative having the formula (1) where n=6, m=4, X=O andR₁=R₂=H (to be termed “CB*[6]” hereinbelow) in 10% yield.

The crystal structure of the obtained cucurbituril derivative wasdetermined by X-ray crystallography. The result is shown in FIG. 2. Asshown in FIG. 2, it was confirmed that the cucurbituril derivativeobtained in Synthesis Example 2 had internal cavities.

¹ H NMR (300 MHz, D₂O): δ=5.73 (d, J=15.9 Hz, 12H), 4.32 (d, J=16.0 Hz,12H), 2.26 (s, 24H), 1.49 (s, 24H); ¹³C NMR (75 MHz, D₂O): δ=156.43,76.51, 44.10, 23.37, 14.07.

SYNTHESIS EXAMPLE 3 Preparation of the Glycoluril Derivative Having theFormula (2) where m=3, X=O, R₁=H

2.0 g of 1 2-cyclopentanedione, 2.9 g of urea, 4 ml of trifluoroaceticacid were dissolved in 60 ml of benzene and refluxed at 80 to 90° C. for16 hours. The water generated during the reaction was removed using aDean-Stark water trap to promote the reaction. The resulting mixture wascooled to room temperature to generate the precipitate which wasfiltered and dried to give a solid glycoluril derivative where m=4, X=Oand R₁=H in 12% yield.

¹ H NMR (300 MHz, DMSO-d₆): δ=7.25 (s, 4H), 1.90 (t, 4H), 1.67(m, 2H),^(13 C NMR ()75 MHz, DMSO-d₆): δ=160.49, 81.70, 40,75, 23.55. MS (ESI):m/z 182.02

SYNTHESIS EXAMPLE 4

The desired product was synthesized by the same method as in SynthesisExample 1, except that a glycoluril derivative with m=1, X=S and R₁=R₂=Hand was used instead of the glycoluril derivative with m=4, X=O andR₁=R₂=H.

SYNTHESIS EXAMPLE 5

The desired product was synthesized by the same method as in SynthesisExample 1, except that a glycoluril derivative with m=2, X=O and R₁=R₂=Hand was used instead of the glycoluril derivative with m=4, X=O andR₁=R₂=H.

SYNTHESIS EXAMPLE 6

The desired product was synthesized by the same method as in SynthesisExample 1, except that a glycoluril derivative with m=3, X=O and R₁=R₂=Hand was used instead of the glycoluril derivative with m=4, X=O andR₁=R₂=H.

SYNTHESIS EXAMPLE 7

The desired product was synthesized by the same method as in SynthesisExample 1, except that a glycoluril derivative with m=5, X=O and R₁=R₂=Hand was used instead of the glycoluril derivative with m=4, X=O andR₁=R₂=H.

SYNTHESIS EXAMPLE 8

The desired product was synthesized by the same method as in SynthesisExample 1, except that a glycoluril derivative with m=7, X=O and R₁=R₂=Hand was used instead of the glycoluril derivative with m=4, X=O andR₁=R₂=H.

By similar methods to Synthesis Examples 1 through 8, the cucurbiturilderivatives were obtained, where m=4, n=7, X=O, R₁=R₂=H; m=4, n=8, X=O,R₁=R₂=H; m=4, n=9, X=O, R₁=R₂=H; m=4, n=10, X=O, R₁=R₂=H; and m=4, n=4,X=O, R₁=R₂=H.

Also, by similar methods to Synthesis Examples 1 through 8, thecucurbituril derivatives were obtained, where m=3, n=7, X=O, R₁=R₂=H;m=3, n=8, X=O, R₁=R₂=H; m=3, n=9, X=O, R₁=R₂=H; m=3, n=10, X=O, R₁=R₂=H;and m=3, n=4, X=O, R₁=R₂=H.

SYNTHESIS EXAMPLE 9

The desired product was synthesized by the same method as in SynthesisExample 1,except that a compound (A) with m=4, X=S and R₁=R₂=H and wasused instead of the compound (A) with m=4, X=O and R₁=R₂=H.

SYNTHESIS EXAMPLE 10

The desired product was synthesized by the same method as in SynthesisExample 1, except that a compound (A) with m=4, X=NH and R₁=R₂=H and wasused instead of the compound (A) with m=4, X=O and R₁=R₂=H. By similarmethods to Synthesis Examples 9 and 10, the cucurbituril derivativeswere obtained, where n=5, m=3, X=S, R₁=R₂=H; n=6, m=3, X=S, R₁=R₂=H;n=7, m=3, X=S, R₁=R₂=H; n=8, m=3, X=S, R₁=R₂=H; n=5, m=4, X=S, R₁=R₂=H;n=6, m=4, X=S, R₁=R₂=H; n=7, m=4, X=S, R₁=R₂=H; n=8, m=4, X=S, R₁=R₂=H;n=5, m=3, X=NH, R₁=R₂=H; n=6, m=3, X=NH, R₁=R₂=H; n=7, m=3, X=NH,R₁=R₂=H; n=8, m=3, X=NH, R₁=R₂=H; n=5, m=4, X=NH, R₁=R₂=H; n=6,m=4,X=NH, R₁=R₂=H; n=7, m=4, X=NH, R₁=R₂=H; and n=8, m=4, X=N H, R₁=R₂=H.

SYNTHESIS EXAMPLE 11 Preparation of the Glycoluril Derivative Having theFormula (2) where m=4, X=O, R₁=H

5.0 g of 1,2-cyclohexanedione, 6.7 g of urea, 10 ml of trifluoroaceticacid were dissolved in 170 ml of benzene and refluxed at 80 to 90° C.for 18 hours. The water generated during the reaction was removed usinga Dean-Stark water trap to promote the reaction. The resulting mixturewas cooled to room temperature to generate the precipitate which wasfiltered and dried to give a solid glycoluril derivative where m=4, X=Oand R₁=R₂=H in 71% yield.

¹ H NMR (300 MHz, DMSO-d₆): δ=7.03 (s, 4H), 1.69 (t, 4H), 1.39(t, 4H);¹³ C NMR (75 MHz, DMSO-d₆): δ=161.19, 74.52, 32.37, 18.43. MS (EI): m/z196.00.

SYNTHESIS EXAMPLE 12

The glycoluril derivative having the formula (2) with m=5, X=O and R₁=Hwas synthesized by the similar method as in Synthesis Example 3.

SYNTHESIS EXAMPLE 13

The glycoluril derivatives having the formula (2) with m=3, X=S andR₁=H; and m=4, X=S and R₁=H were synthesized by the similar method as inSynthesis Example 3.

SYNTHESIS EXAMPLE 14

The glycoluril derivatives having the formula (2) with m=3, X=NH andR₁=H; and m=4, X=NH and R₁=H were synthesized by the similar method asin Synthesis Example 3.

Solubilities of the cucurbituril derivatives synthesized in Examples 1and 2 were measured in water, methanol, dimethylsulfoxide andacetonitrile, and the result is shown in Table 1.

TABLE 1 Solvent CB*[5] CB*[6] Water 2.6 × 10⁻¹M 1.7 × 10⁻¹M Methanol 3.1× 10⁻²M 4.3 × 10⁻¹M Dimethylsulfoxide 1.8 × 10⁻²M 3.9 × 10⁻¹MAcetonitrile 6.7 × 10⁻⁴M 2.1 × 10⁻¹M

As shown in Table 1, the cucurbituril derivatives obtained in SynthesisExamples 1 and 2 have good solubility in water at a neutral pH andorganic solvents and have internal cavities, which was confirmed byX-ray crystal structure determination. Thus, inclusion complexes withorganic compounds can be effectively produced, which has been verifiedin the following examples.

EXAMPLE 1

6.6 mg of CB*[6] synthesized in Synthesis Example 2 and 10 mltetrahydrofuran were dissolved in 0.5 ml of D₂O. NMR spectroscopyconfirms quantitative formation of a 1:1 host-guest complex.

¹ H NMR (D₂O, 500 MHz): δ=5.72 (d, 12H), 4.26 (d, 12H), 2.86 (m, 4H), 2.23 (s, 24H), 1.46 (s, 24H), 1.01 (m, 4H)

EXAMPLE 2

6.6 mg of CB*[6] synthesized in Synthesis Example 2 and 10 ml ofcyclopentane were dissolved in 0.5 ml of D₂O. NMR spectroscopy confirmsquantitative formation of a 1:1 host-guest complex.

¹ H NMR (D₂O, 500 MHz): δ=5.77 (d, J=15.0 Hz, 12H), 4.22 (d, J=16.0 Hz,12H), 2.23 (s, 24H), 1.45 (s, 24H), 0.70 (s, 10H).

EXAMPLE 3

6.6 mg of CB*[6] synthesized in Synthesis Example 2 and 1.2 mg ofparatoluidine were dissolved in 0.5 ml of D₂O. NMR spectroscopy confirmsquantitative formation of a 1:1 host-guest complex.

¹ H NMR (D₂O, 500 MHz): δ=6.63 (d, 2H), 6.52 (d, 2H), 5.73 (dd, 12H), 4.19 (dd, 12H), 2.25 (s, 24H), 2.11 (s, 3H), 1.45 (s, 24H).

EXAMPLE 4

6.6 mg of CB*[6] synthesized in Synthesis Example 2 and 1.5 mg ofparatoluidine hydrochloride were dissolved in 0.5 ml of D₂O. NMRspectroscopy confirms quantitative formation of a 1:1 host-guestcomplex.

¹ H NMR (D₂O, 500 MHz): δ=6.65 (d, 2H), 6.53 (d, 2H), 5.73 (dd, 12H), 4.19 (t, 12H), 2.20 (s, 24H), 2.05 (s, 3H), 1.46 (s, 24H).

EXAMPLE 5

6.6 mg of CB*[6] synthesized in Synthesis Example 2 and 1.2 mg of1,4-phenyline diamine were dissolved in 0.5 ml of D₂O. NMR spectroscopyconfirms quantitative formation of a 1:1 host-guest complex.

¹ H NMR (D₂O, 500 MHz): δ=6.21 (d, 4H), 5.79 (d, 12H), 4.26 (d, 12H), 2.26 (s, 24H), 1.51 (s, 24H).

The above results of Examples 1 through 5 show that the cucurbiturilderivatives obtained in Synthesis Examples 1 and 2 are advantageouslyused in extraction, separation and purification of the organic materialsused in the examples.

The cucurbituril derivative obtained in Synthesis Example 2 is capableof forming a gaseous inclusion complex in its cavities, which has beenverified in Example 6.

EXAMPLE 6

6.6 mg of CB*[6] synthesized in Synthesis Example 2 was dissolved in 0.5ml of D₂O and isobutene gas was inspired into the resultant product for10 minutes. NMR spectroscopy confirms quantitative formation of a 1:1host-guest complex.

¹ H NMR (D₂O, 500 MHz): δ=5.77 (d, 12H), 4.26 (d, 12H), 3.90 (s, 2H),2.26 (s, 24H), 1.50 (s, 24H), 1.00 (s, 6H).

The result of Example 6 shows that the cucurbituril derivative obtainedin Synthesis Example 2 can be advantageously used in extraction,separation and purification of the gaseous molecules used in theexamples, and detection of other contaminants in the air.

The following example is for investigating whether the cucurbiturilderivatives can effectively transport physiologically active materialsor drugs. In the example, acetylcholine chloride, a neurotransmitter,was used.

EXAMPLE 7

6.6 mg of CB*[6] synthesized in Synthesis Example 2 and 2.0 mg ofacetylcholine chloride were dissolved in 0.5 ml of D₂O. NMR spectroscopyconfirms quantitative formation of a 1:1 host-guest complex.

¹ H NMR (D₂O, 500 MHz): δ=5.81 (dd, 12H), 4.27 (dd, 12H), 3.99 (s, 2H),3.8 (s, 2H), 3.36 (s, 9H), 2.27 (s, 24H), 1.46 (s, 24H), 1.15 (s, 3H).

On the other hand, the cucurbituril derivative obtained in SynthesisExample 1 has Lewis base atoms near the cavities of the molecule, andthus they can effectively form a complex with positively charged metalions or other organic ions. The following example is for investigatingwhether the cucurbituril derivatives having this property can be appliedin manufacturing sensors for sensing positive metal ions or ammoniumions.

EXAMPLE 8

A 5.5 mM CB*[5] solution and 110 mM-KCl solution were prepared with 0.05M tris buffered solution having a pH of 7.2. Then, the binding constantof CB*[5] was measured using a microcalorimeter (VP-ITC, manufactured byMicroCal). As a result, CB*[5] forms a 1:2 complex with potassium ionswith a primary binding constant of 2.8×10⁴ M⁻¹ and a secondary bindingconstant of 1.5×10² M⁻¹. CB*[5] can selectively bind with alkali metalions, as well as with ammonium ions. The result confirms thatcucurbituril derivatives can be used as ion sensors.

The following example is for investigating whether ammonium ions presentin an organic solvent can bind with CB*[5].

EXAMPLE 9

5.5 mg of CB*[5] synthesized in Synthesis Example 1 and 6.7 mg of(NH₄)⁺(BPh₄)³¹ were dissolved in 0.5 ml of CD₃CN. NMR spectroscopyconfirms binding of ammonium ions of (NH₄)⁺(BPh₄)⁻with CB*[5] at anequivalent ratio of 2:1.

¹ H NMR (CD₃CN, 500 MHz):δ=7.24 (s, 16H), 6.99 (t, 16H), 6.84 (t, 8H),6.21 (brs, 8H), 5.55 (d, 10H), 4.09 (d, 10H), 2.04 (s, 20H), 1.36 (s,20H).

The following example is for investigating selectivity to detrimentalheavy metal ions such as lead ions using an ion selective electrodehaving an ion selective membrane by a preparation method of the ionselective electrode using CB*[5] prepared in Synthesis Example 1.

EXAMPLE 10

A solution obtained by dissolving 1 wt % of CB*[5] prepared in SynthesisExample 1 in 0.1 mL of methanol and a 0.4 mL tetrahydrofuran solutionobtained by dissolving 33 wt % of polyvinylchloride, a polymer support,65.6 wt % of 2-nitrophenyloctylether, a plasticizer, and 0.4 wt % ofpotassium tetrakis(4-chlorophenyl)borate, were homogenously mixed and asolvent was then removed slowly to form an ion selective membrane. Anion selective electrode was manufactured using the ion selectivemembrane. Here, a silver chloride coated Ag wire immersed in 0.05 M KClaqueous solution was used as a reference electrode.

The reference electrode and the ion selective electrode were immersed in250 mL of a 1 mM Mg(OAc)₂-HCl buffered solution having a pH of 4 and theresultant product was kept stirring at least one hour until the layerexhibited a stable boundary potential. Thereafter, potential differenceswere measured while increasing the concentration of lead ions by 10folds from 10⁻⁶ M to 10⁻³ M using a micro pipet at intervals of 100seconds. Selectivities to lead ions were measured by a fixed solutionmethod at a concentration of 0.01 M. The measurement result is given inFIG. 3 and Table 2.

FIG. 3 is a graphical representation of lead ions, potassium ions,ammonium ions and sodium ions sensed from an ion selective electrodeprepared using a cucurbituril derivative CB*[5] prepared in SynthesisExample 1 of the present invention, and Table 2 shows selectivities forthese ions.

TABLE 2 Selectivity Detection Ions analyzed (log K_(Pb2+)) limit (mol/L)Pb²⁺ 0 2.5 × 10⁻⁷ K⁺ −1.2 6.0 × 10⁻⁵ NH₄ ⁺ −1.8 4.0 × 10⁻⁴ Na⁺ −2.3 5.3× 10⁻⁴

The results shown in FIG. 3 and Table 2 show that the ion selectiveelectrode manufactured using CB*[5] prepared in Synthesis Example 1 canbe used to detect detrimental heavy metal ions such as lead ions ormercury ions remaining in water.

The following example is for investigating selectivity to acetylcholine,a neurotransmitter, using an ion selective electrode having an ionselective membrane by a preparation method of the ion selectiveelectrode using CB*[6] prepared in Example 1.

EXAMPLE 11

A solution obtained by dissolving 1 g of CB*[6] prepared in Example 1 in0.1 mL of methanol and a 0.4 mL tetrahydrofuran solution obtained bydissolving 33 g of polyvinylchloride, a polymer support, 65.6 g of2-nitrophenyloctylether, a plasticizer, and 0.4 g of potassiumtetrakis(4-chlorophenyl)borate, were homogenously mixed and a solventwas then removed slowly to form an ion selective membrane. An ionselective electrode was manufactured using the ion selective membrane.Here, a silver chloride coated Ag wire immersed in 0.05 M KCl aqueoussolution was used as a reference electrode.

The reference electrode and the ion selective electrode were immersed in250 mL of a 0.05 M Tris-HCl buffered solution having a pH of 7.2 and theresultant product was kept stirring at least one hour until the layerexhibited a stable boundary potential. Thereafter, potential differenceswere measured while increasing the concentration of lead ions by 10folds from 10⁻⁶ M to 10⁻¹ M using a micro pipet at intervals of 100seconds. Selectivities to lead ions were measured by a fixed solutionmethod at a concentration of 0.01 M. The measurement result is given inFIG. 4 and Table 3.

FIG. 4 is a graphical representation of lead ions, potassium ions,ammonium ions and sodium ions sensed from an ion selective electrodeprepared using a cucurbituril derivative CB*[6] prepared in Example 1 ofthe present invention, and Table 3 shows selectivities-for these ions.

TABLE 3 Selectivity Detection Ions analyzed (log K_(Acetylcholine))limit (mol/L) Acetylcholine 0 6.3 × 10⁻⁷ Choline −1.2  8.3 × 10⁻¹¹ K⁺−2.7 6.9 × 10⁻⁵ NH₄ ⁺ −3.1 5.2 × 10⁻⁴ Na⁺ −3.9 3.2 × 10⁻⁴

The results shown by Example 11 show that the ion selective electrodemanufactured using CB*[6] prepared in Example 1 can selectivelyrecognize a neurotransmitter in vivo, e.g., acetylcholine, to be usedfor clinical analysis.

As described above, since the cucurbituril derivatives having theformula (1) according to the present invention, are soluble in water ata neutral pH or in methanol, a common organic solvent, they have widerapplications than conventional cucurbituril derivatives. Also, thecucurbituril derivatives can encapsulate various compounds withdifferent sizes, and have Lewis base atoms near the entrances to theircavities so that they can form complexes with metal ions, organometallicions or positively charged organic compounds. With these features, thecucurbituril derivatives according to the present invention have verywide applications. In addition, the preparation of the cucurbiturilderivatives according to the present invention is easily scaled up forindustrial purposes. In the cucurbituril derivative preparationaccording to the present invention, each cucurbituril derivative can beseparated from the mixture containing the cucurbituril derivativeshaving the formula (1), where n is a value from 4 to 20, and a mixtureof two or more of the cucurbituril derivatives can also be obtained.

The cucurbituril derivatives and the mixture thereof disclosed by thepresent invention are applied to remove organic dyes from waste water,heavy metal from water and radioactive isotopes from radioactive wastes,to capture and remove unpleasant odor, and air pollutants such as carbonmonoxide, carbon dioxide, NO_(x) and SO_(x), and to deodorize anddecolorize livestock waste water and ironwork waste water. Also, thecucurbituril derivatives disclosed by the present invention areapplicable in manufacturing sensors for sensing ammonium ions, organicamines, amino acid derivatives, nucleic acid bases, alkali metal oralkaline earth metal ions. The cucurbituril derivatives can be used asadditives to polymers, cosmetics, artificially scented papers ortextiles, pesticides, drugs and foods, and used as drug carriers. Thecucurbituril derivatives having the formula (1) can be used forextraction and purification of fullerene or caborane compounds, and usedas packing materials of chromatographic columns, as additives to gasseparation membranes, as catalysts for various chemical reactions. Inparticular, since the cucurbituril derivatives according to the presentinvention are soluble in water at a neutral pH, they can beadvantageously used in recognizing physiologically active materials invivo, e.g., acetylcholine. Also, since increased solubility of thecucurbituril derivatives in organic solvents makes it easy tomanufacture ion selective electrode membranes, the cucurbiturilderivatives can be used for development of ionic sensors directlyapplicable for clinical analysis or detection of environmentalpollutants. In addition, use of the mixture of cucurbituril derivativesprepared by the method shown in FIG. 1 without separation isadvantageous in terms of cost, and can be readily adapted for industrialuses.

Also, the glycoluril derivatives having the formula (2) can beadvantageously used in preparing the cucurbituril derivatives having theformula (1).

While the present invention has been particularly shown and describedwith reference to exemplary embodiments thereof, it will be understoodby those of ordinary skill in the art that various changes in form anddetails may be made therein without departing from the spirit and scopeof the present invention as defined by the following claims.

1. A cucurbituril derivative having the formula (1):

where X is O, S or NH; R₁ and R₂ are methyl; and n and m areindependently integers from 4 to 10 and from 1 to 7, respectively. 2.The cucurbituril derivative according to claim 1, wherein X=O and n is avalue of 4 to 10 and m is a value of 1 to
 7. 3. The cucurbiturilderivative according to claim 1, wherein X=NH or S and n is a value of 4to 10 and m is a value 1 of
 7. 4. A method for preparing a cucurbiturilderivative having the formula (1), comprising:

(a-2) mixing and stirring a compound having the formula (2) and analdehyde compound having the formula (A); and (b-2) adding acid to thereaction mixture and stirring to complete the reaction, where X is O, Sor NH; R₁ and R₂ are methyl; and n and in are independently integersfrom 4 to 10 and from 1 to 7, respectively.
 5. The method according toclaim 4, wherein in step (a-2), the acid is added in an amount of 3 to 7moles and the aldehyde compound having the formula (A) is added in anamount of 2 to 20 moles with respect to 1 mole of the compound havingthe formula (2), and the reaction temperature is in the range of 50 to150° C.
 6. The method according to claim 4, wherein in step (b-2), thereaction temperature is in the range of 50 to 150° C.
 7. The methodaccording to claim 4, wherein in step (a-2), the acid is selected fromthe group consisting of hydrochloric acid, sulfuric acid, phosphoricacid, acetic acid and nitric acid and is used as a diluted solution inwater or an organic solvent.
 8. The method according to claim 4, whereinamong reaction products of step (b-2), the cucurbituril derivative withn=5 is produced in a yield of 15 to 50%, the cucurbituril derivativewith n=6 is produced in a yield of 2 to 10%, and the cucurbiturilderivatives with n=4 and 7 to 10 are produced in a yield of 1 to 5%,respectively.
 9. A The method according to claim 4, further comprisingseparating the cucurbituril derivative having the formula (1) from thecucurbituril derivative mixture by fractional crystallization.
 10. Themethod according to claim 9, wherein at least one solvent selected fromthe group consisting of water, acetone and acetonitrile is used in thefractional crystallization.